Rotigotine is chemically known as (6S)-6-{propyl [2-(2-thienyl)ethyl]amino}-5,6,7,8-tetrahydro-1-naphthalenol having the formula (I) as mentioned below.

Rotigotine is marketed as Neupro in US and Europe for the treatment of Parkinson's disease. Rotigotine was first disclosed in the U.S. Pat. No. 4,564,628.
The U.S. Pat. No. 4,564,628 discloses two processes for the preparation of Rotigotine. One of the processes is depicted in Scheme-1.

In this scheme, the compound 1,2,3,4-tetrahydro-5-methoxy-N-propyl-N-[2-(2-thienyl)ethyl]-2-naphthaleneamine (A) is prepared from the reaction of 1,2,3,4-tetrahydro-5-methoxy-N-[2-(thienyl)-ethyl]-2-naphthaleneamine with propionyl chloride to form an intermediate followed by the reduction of the formed intermediate. The compound 1,2,3,4-tetrahydro-5-methoxy-N-propyl-N-[2-(2-thienyl)ethyl]-2-naphthaleneamine (A) is then demethylated to form racemic Rotigotine.
Another process involves the preparation of the intermediate 1,2,3,4-tetrahydro-5-methoxy-N-propyl-N-[2-(2-thienyl)ethyl]-2-naphthaleneamine (A) from the reaction of 1,2,3,4-tetrahydro-5-methoxy-N-propyl-2-naphthaleneamine with 2-thienylacetic acid in presence of borane trimethylamine complex as depicted in Scheme-2. The prepared intermediate (A) in this process is then demethylated to form Rotigotine.

The transformation of intermediate (A) into Rotigotine involves the demethylation of compound (A) in the presence of boron tribromide at low temperature in inert solvents. After the completion of this reaction, the excess boron tribromide was destroyed by addition of methanol.
The use of 48% hydrobromic acid for the demethylation of the compound (A) reported in literature, yielded N-dealkylated impurities along with Rotigotine. The structural similarity of the impurities and Rotigotine makes the purification problematic through physical methods.
The use of boron tribromide for the demethylation of the compound (A) to obtain Rotigotine reported in literature, has to be carried out at low temperatures of −30° C. to −40° C. Performing reaction at such low temperatures and cumbersome processes involving the treatment of excess of boron tribromide makes this process less preferable on commercial scale.
The use of aluminium chloride along with thiourea for the demethylation of the compound (A) to obtain Rotigotine as disclosed in the International Publication No. 2010073124 results in Rotigotine with impurities. These impurities formed at this stage are not easy to purify from Rotigotine. Further multiple stages of purification of Rotigotine from these impurities causes yield loss in the final API.
The U.S. Pat. No. 4,885,308 discloses a process for preparation of Rotigotine involving the resolution of racemic 2-(N-propylamino)-5-methoxytetralin to get desired enantiomer and then converting the desired enantiomer to Rotigotine, using the process disclosed in U.S. Pat. No. 4,564,628.
The U.S. Pat. No. 6,372,920 discloses a process for preparing Rotigotine involving the step of reacting (−)-5-hydroxy-N-n-propyl-2-aminotetralin with 2-(2-thienyl)ethanol toluene sulfonate in the presence of alkali metal carbonate or alkali metal bicarbonate.

The U.S. Pat. No. 8,519,160 discloses a process for the preparation of Rotigotine involving the steps of (i) demethylation of 2-N-propyl-5-methoxy tetraline by the treatment with 48% hydrobromic acid to obtain 2-N-propyl-5-hydroxy tetraline base; and (ii) the reaction of the obtained 2-N-propyl-5-hydroxy tetraline base with 2-thienylacetic acid-sodium borohydride complex in toluene to obtain Rotigotine free base.

Bromo impurities formed during the demethylation of the compound 2-N-propyl-5-methoxy tetraline using 48% hydrobromic acid to obtain 2-N-propyl-5-hydroxy tetraline base are difficult to remove from the obtained 2-N-propyl-5-hydroxy tetraline base.
The U.S. Pat. No. 8,614,337 discloses a method for preparing Rotigotine which involves the steps of: (i) resolution of racemic to obtain (S)-5-methoxy-N-2′-(thien-2-yl-)ethyl-tetralin-2-amine; and (ii) reaction of the resolved enantiomer with iodopropane in presence of base to yield (S)-5-methoxy-N-propyl-N-(2′-(thien-2-yl-)ethyl)-tetralin-2-amine (A) and (iii) demethylation of the compound (S)-5-methoxy-N-propyl-N-(2′-(thien-2-yl-)ethyl)-tetralin-2-amine (A) to obtain Rotigotine.

Besides the availability of different processes for the preparation Rotigotine in state of the art, there is a need for alternative process for the preparation of Rotigotine that would be economically significant than the others.